Publications by authors named "Gianfranco Ferraccioli"

217 Publications

Retention rate of a second line with a biologic DMARD after failure of a first-line therapy with abatacept, tocilizumab, or rituximab: results from the Italian GISEA registry.

Clin Rheumatol 2021 Apr 21. Epub 2021 Apr 21.

Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari, Bari, Italy.

Objectives: EULAR recommendations do not suggest which biologic disease-modifying anti-rheumatic drug (bDMARD) should be preferred after failure of a first bDMARD in the treatment of rheumatoid arthritis (RA). In particular, few data are available regarding the effectiveness of a second-line bDMARD after failure of abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX). The aim of this study was to analyze the retention rate of a second line with tumor necrosis factor inhibitors (TNFi) or other mechanisms of action (MoAs), after the failure of either RTX, TCZ, or ABA.

Methods: Two hundred and seventy-eight RA patients from the Italian GISEA registry were included in the study. RTX was the first bDMARD in 18% of patients, ABA in 45.7%, and TCZ in 36.3%, while the second bDMARD was a TNFi (group 1) in 129 patients and an agent with a different MoA (group 2) in 149.

Results: During a median follow-up of 22 months (IQR 68), 129 patients discontinued their treatment; patients of group 1 discontinued the treatment more frequently than patients of group 2 (p<0.001) with retention rates of 33.6±5.7% and 63.6±4.6% after 104 weeks for group 1 and group 2, respectively (p<0.001). At multivariate analysis, the mechanism of action was the only predictor for the maintenance in therapy.

Conclusions: According to our data, ABA, RTX, and TCZ seem to maintain a good retention rate also when used as a second-line therapy, suggesting their use after the failure of a non-TNFi as first-line therapy. However, specifically designed studies are needed to evaluate the more appropriate therapeutic strategies in RA, according to the first-line drug, including new targeted synthetic DMARDs. Key Points • A large proportion of rheumatoid arthritis patients fail the first biologic DMARD. • Few data are available about the efficacy of biologic DMARD after the failure of a non-TNF inhibitor. • Abatacept, rituximab, or tocilizumab seem to maintain a good retention rate after the failure of a first-course therapy with a non-TNF inhibitor.
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http://dx.doi.org/10.1007/s10067-021-05734-3DOI Listing
April 2021

Synovial tissue derived characteristics are included in a nomogram for the prediction of treatment response in naïve Rheumatoid Arthritis.

Arthritis Rheumatol 2021 Mar 22. Epub 2021 Mar 22.

Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Objectives: This study aims to apply the synovitis assessment in routine care of naïve Rheumatoid Arthritis (RA) and to develop a multiparametric nomogram for baseline diagnostic and treatment response prediction.

Methods: 1015 patients [545 RA, 167 Psoriatic Arthritis (PsA), 199 Undifferentiated Peripheral Inflammatory Arthritis (UPIA), 18 crystal arthritis, 26 connective tissue diseases and 60 osteoarthritis (OA)] undergoing ultrasound (US)-guided synovial tissue (ST) biopsy were enrolled (SYNGem) and stratified based on disease phase. The Krenn synovitis score(KSS) was assessed and integrated with disease characteristics and clinical outcome and a nomogram was created incorporating predictors of "DAS-Remission achievement at 6 months" in naïve RA treated with a treat to target strategy.

Results: KSS significantly differs among patients with RA, as well as PsA and UPIA, when compared to OA. In RA, KSS directly correlated with DAS28 and was related to autoantibody positivity in naïve RA. Moreover, naïve RA achieving 6 months DAS-remission had, at baseline, lower KSS, shorter symptoms duration (VERA) and lower disease activity than naïve RA not achieving DAS-remission. On logistic regression, being VERA, not having high disease activity and having a KSS<5 at baseline, were synergistic factors of DAS-remission achievement at 6 months and a nomogram integrating baseline clinical and histological characteristics of naïve RA enabled to predict up to 81.7% of probability to achieve 6 months DAS-remission.

Conclusion: KSS is a reliable tool for synovitis assessment on US-guided ST biopsies being contingent on disease phase, autoimmune profile and integrated within a therapeutic response predictive nomogram in naïve RA.
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http://dx.doi.org/10.1002/art.41726DOI Listing
March 2021

Systemic Bone Density at Disease Onset Is Associated With Joint Erosion Progression in Early Naive to Treatment Rheumatoid Arthritis: A Prospective 12-Month Follow-Up Open-Label Study.

Front Med (Lausanne) 2021 25;8:613889. Epub 2021 Feb 25.

Division of Rheumatology, Università Cattolica del Sacro Cuore, Rome, Italy.

Osteoporosis and bone erosions are hallmarks of rheumatoid arthritis (RA) since disease onset is underpinned by the inflammatory burden. In this observational study, we aimed to dissect the putative RA-related parameters and bone-derived biomarkers associated with systemic and focal bone loss at disease onset and with their progression. One-hundred twenty-eight patients with early rheumatoid arthritis (ERA) were recruited at disease onset. At study entry, demographic, clinical, and immunological parameters were recorded. Each ERA patient underwent plain X-rays of the hands and feet at study entry and after 12 months to assess the presence of erosions. After enrollment, each patient was treated according to the recommendations for RA management and followed up based on a treat-to-target (T2T) strategy. At baseline, blood samples for soluble biomarkers were collected from each patient, and plasma levels of osteoprotegerin (OPG), receptor activator of nuclear factor κB ligand (RANKL), Dickkopf-1 (DKK1), and interleukin 6 (IL-6) were assessed by enzyme-linked immunosorbent assay (ELISA). Seventy-one ERA patients underwent bone mineral density (BMD) measurement at the left femoral neck and second to fourth lumbar spine vertebrae (L2-L4) by dual-energy X-ray absorptiometry (DXA). Among the whole cohort, 34 (26.6%) ERA patients with bone erosions at study entry had a higher disease activity ( = 0.02) and IL-6 plasma levels ( = 0.03) than non-erosive ones. Moreover, at DXA, 33 (46.5%) ERA patients had osteopenia, and 16 (22.5%) had osteoporosis; patients with baseline bone erosions were more likely osteopenic/osteoporotic than non-erosive ones ( = 0.03), regardless of OPG, RANKL, and DKK1 plasma levels. Obese ERA patients were less likely osteopenic/osteoporotic than normal weight ones ( = 0.002), whereas anti-citrullinated protein antibodies (ACPA) positive ERA patients were more likely osteopenic/osteoporotic than ACPA negative ones ( = 0.034). At logistic regression analysis, baseline Disease Activity Score measured on 44 joints (DAS44) [OR: 2.46 (1.11-5.44)] and osteopenic/osteoporosis status [OR: 7.13 (1.27-39.94)] arose as independent factors of erosiveness. Baseline osteopenic/osteoporotic status and ACPA positivity were associated with bone damage progression during the follow-up. Bone erosions presence is associated with systemic bone loss since the earliest phases of RA, suggesting that the inflammatory burden and autoimmune biology, underpinning RA, represent crucial enhancers of bone remodeling either locally as at systemic level.
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http://dx.doi.org/10.3389/fmed.2021.613889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959810PMC
February 2021

Rituximab Followed by Belimumab Controls Severe Lupus Nephritis and Bullous Pemphigoid in Systemic Lupus Erythematosus Refractory to Several Combination Therapies.

Front Med (Lausanne) 2020 28;7:553075. Epub 2020 Oct 28.

Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Systemic lupus erythematosus (SLE) and bullous pemphigoid (BP) are chronic autoimmune diseases in which B cells play an important pathogenic role in the different stages of the disease. B cell-targeted therapies have been suggested as a new rational approach for treating SLE. Rituximab (RTX), an anti-CD20 chimeric monoclonal antibody, failed to achieve primary endpoints in two clinical trials (EXPLORER and LUNAR) despite multiple observational and retrospective studies showing its beneficial effect on SLE. Moreover, RTX is recommended in cases of BP that is unresponsive to conventional treatments. Belimumab (BLM), a human immunoglobulin G1 λ monoclonal antibody that inhibits soluble B-lymphocyte stimulator (BlyS)/B-cell activating factor (BAFF), is the only biological treatment approved for standard therapy of refractory autoantibody-positive active SLE. Animal models and a few case reports have supported the efficacy of the combined use of RTX followed by BLM as maintenance therapy in severe lupus nephritis (LN), suggesting that their combined use may be more effective than their single use, without compromising safety. In this study, we describe the clinical case of a SLE patient with predominant renal involvement in overlap with BP, refractory to conventional therapy including RTX alone, achieving significant steroid sparing and clinical remission under sequential treatment of RTX-BLM. Moreover, we describe the first case of BP successfully treated with BLM. This case report may encourage further clinical research studies in B lymphocyte targeted combination therapy in patients affected by SLE with major organ involvement or with refractory disease, suggesting that RTX and BLM sequential therapy may be a valid option for the treatment of SLE manifestations, including conventional therapy and RTX-resistant LN.
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http://dx.doi.org/10.3389/fmed.2020.553075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657367PMC
October 2020

Correspondence on 'Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis'.

Ann Rheum Dis 2020 Nov 3. Epub 2020 Nov 3.

Department of Medical and Surgical Sciences, Division of Rheumatology, Catholic University of the Sacred Heart, Rome, Lazio, Italy

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http://dx.doi.org/10.1136/annrheumdis-2020-219309DOI Listing
November 2020

EULAR definition of difficult-to-treat rheumatoid arthritis.

Ann Rheum Dis 2021 01 1;80(1):31-35. Epub 2020 Oct 1.

Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands.

Background: Despite treatment according to the current management recommendations, a significant proportion of patients with rheumatoid arthritis (RA) remain symptomatic. These patients can be considered to have 'difficult-to-treat RA'. However, uniform terminology and an appropriate definition are lacking.

Objective: The Task Force in charge of the Development of EULAR recommendations for the comprehensive management of difficult-to-treat rheumatoid arthritis" aims to create recommendations for this underserved patient group. Herein, we present the definition of difficult-to-treat RA, as the first step.

Methods: The Steering Committee drafted a definition with suggested terminology based on an international survey among rheumatologists. This was discussed and amended by the Task Force, including rheumatologists, nurses, health professionals and patients, at a face-to-face meeting until sufficient agreement was reached (assessed through voting).

Results: The following three criteria were agreed by all Task Force members as mandatory elements of the definition of difficult-to-treat RA: (1) Treatment according to European League Against Rheumatism (EULAR) recommendation and failure of ≥2 biological disease-modifying antirheumatic drugs (DMARDs)/targeted synthetic DMARDs (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated); (2) presence of at least one of the following: at least moderate disease activity; signs and/or symptoms suggestive of active disease; inability to taper glucocorticoid treatment; rapid radiographic progression; RA symptoms that are causing a reduction in quality of life; and (3) the management of signs and/or symptoms is perceived as problematic by the rheumatologist and/or the patient.

Conclusions: The proposed EULAR definition for difficult-to-treat RA can be used in clinical practice, clinical trials and can form a basis for future research.
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http://dx.doi.org/10.1136/annrheumdis-2020-217344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788062PMC
January 2021

Gut microbiota analysis in systemic sclerosis according to disease characteristics and nutritional status.

Clin Exp Rheumatol 2020 May-Jun;38 Suppl 125(3):73-84. Epub 2020 Aug 26.

Institute of Rheumatology, Università Cattolica del Sacro Cuore, and Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Objectives: Systemic sclerosis (SSc) is a rare multi-organ disorder with a prominent gastrointestinal (GI) involvement. Altered gut microbiota is now considered a pivotal factor associated with the development of immune-mediated and inflammatory diseases. We performed a 16S ribosomal RNA (rRNA) gene-sequencing analysis of fecal microbiota in a cohort of SSc patients and matched healthy controls (HCs), with the aim to obtain some hints about a possible role of dysbiosis in the onset, progression, and severity of the disease.

Methods: We analysed stool samples from 63 SSc patients with different disease duration, phenotype, and nutritional status and from 17 HCs through 16S ribosomal RNA (rRNA) gene-sequencing.

Results: Microbial richness was lower for patients with long-standing disease. A similar observation was made for patients with diffuse cutaneous SSc (dsSSc) compared to those with limited variant (lcSSc) and for patients who reported a recent weight loss. Consistent with previous reports, we noted a deviation of the intestinal microbial composition in patients with SSc compared to HCs, with a greater expression of Lactobacillus and Streptococcus and a depletion of Sutterella. Nutritional status, assessed using BMI as a surrogate, appeared to have a marked impact on the gut microbiota, with overweight patients showing lower richness compared both to underweight and normal-BMI patients.

Conclusions: Our findings expand the current knowledge of gut microbiota in SSc and could be useful to identify patients who would most benefit from treatments aimed at restoring the eu-biosis.
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September 2020

Factors Predicting Early Failure of Etanercept in Rheumatoid Arthritis: An Analysis From the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis) Registry.

Arch Rheumatol 2020 Jun 7;35(2):163-169. Epub 2020 Feb 7.

Department of Medicine, Rheumatology Unit, University of Bari, Interdisciplinary Bari, Italy.

Objectives: This study aims to investigate the factors associated with early discontinuation (within one year) of etanercept (ETA) in rheumatoid arthritis (RA) patients who began ETA as first biologic disease-modifying antirheumatic drug (bDMARD) and who were entered into the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis; GISEA) registry.

Patients And Methods: This registry-based cohort study included 477 RA patients (95 males, 382 females; median age 53 years; range 18 to 83 years) who began ETA as first bDMARD. Patient demographics, disease features and drugs were re-evaluated after 12 months. Baseline predictors of ETA discontinuation were estimated by univariate and multivariate analyses using Cox regression model.

Results: Seventy patients (14.7%) discontinued ETA during the first year (for inefficacy in 55.8%, adverse events in 28.6%, and other reasons in 6.5%). Concurrent conventional synthetic DMARDs (csDMARDs) were reported in 54.3% of patients, mainly methotrexate (MTX), while 52.4% of subjects took low doses of glucocorticoids. Patients stopping ETA more frequently showed one or more comorbidities, mainly cardiovascular diseases (28.6% vs. 15.7% in patients stopping and continuing ETA, respectively, p=0.009). The presence of comorbidities and a combination therapy with csDMARDs other than MTX were independent factors associated with early discontinuation of ETA at multivariate Cox analysis.

Conclusion: Although ETA demonstrated a high persistence in biologic-naïve RA patients, about 15% of patients discontinued the treatment within 12 months. The presence of comorbidities and a combination therapy with csDMARDs other than MTX were the main factors for an early withdrawal of the drug.
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http://dx.doi.org/10.46497/ArchRheumatol.2020.7499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406167PMC
June 2020

Pulmonary intravascular coagulopathy in COVID-19 pneumonia.

Lancet Rheumatol 2020 Aug 29;2(8):e458. Epub 2020 Jun 29.

Division of Rheumatology, School of Medicine, Catholic University Sacred Heart, Rome, Italy.

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http://dx.doi.org/10.1016/S2665-9913(20)30189-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324089PMC
August 2020

Golimumab effectiveness in biologic inadequate responding patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis in real-life from the Italian registry GISEA.

Joint Bone Spine 2021 01 2;88(1):105062. Epub 2020 Aug 2.

Rheumatology, UOC Reumatologia, AOUI Verona, Verona, Italy.

Objective: To evaluate the clinical effectiveness of golimumab in biologic inadequate responder (IR) patients with Rheumatoid arthritis (RA), Spondyloarthritis (SpA), and Psoriatic arthritis (PsA).

Methods: We analyzed 1424 patients on golimumab from the GISEA registry. Drug survival was estimated by Kaplan-Meier analysis in biologic-naïve, 1-biologic IR, ≥2-biologics IR patients. Hazard ratios (HRs) of discontinuing golimumab at 2 years were assessed by multivariate Cox regression. Patients achieving CDAI based low disease activity (LDA) or BASDAI<4 were calculated at 6 and 12 months.

Results: In RA (n.370), the 2-years survival on golimumab was 61.4% in 1-biologic IR, 51.9% in≥2-biologics IR, and 73.1% in biologic-naive patients (P=0.002 vs≥2-biologics IR). In SpA (n.502), the survival was similar among 1-biologic IR (80%), ≥2-biologics IR (76.5%), and biologic-naive (74.6%) patients (P>0.05). In PsA (n.552) the survival was 72% in 1-biologic IR, 72.5% in≥2-biologics IR, and 71.8% in naïve-biologic (P>0.05). Predictors of golimumab discontinuation were monotherapy (HR 1.65) for RA, female gender for SpA (HR 2.48) and PsA (HR 1.57). In RA, patients on CDAI-LDA were lower in 1-biologic IR (40%) or≥2 biologics IR (40%) than in biologic-naïve (60%) group at 6 months (P=0.02), but no difference was observed at 12 months. In PsA and SpA, the percentage of patients on CDAI-LDA or BASDAI<4 at 6 months was almost identical across the subgroups.

Conclusions: Golimumab had similar effectiveness in biologic-failure and biologic-naïve SpA and PsA, but seems to be less effective in multi-failure RA patients, especially as monotherapy. The best outcomes were seen in male patients.
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http://dx.doi.org/10.1016/j.jbspin.2020.07.011DOI Listing
January 2021

More evidences on which biologic and which pathway is key in severe-critical COVID-19 pneumonia.

Ann Rheum Dis 2020 Jul 31. Epub 2020 Jul 31.

Department of Rheumatology, Policlinico Universitario Agostino Gemelli, Universita' Cattolica del Sacro Cuore, Roma, Lazio, Italy

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http://dx.doi.org/10.1136/annrheumdis-2020-218523DOI Listing
July 2020

Basic immunology may lead to translational therapeutic rationale: SARS-CoV-2 and rheumatic diseases.

Eur J Clin Invest 2020 Sep 29;50(9):e13342. Epub 2020 Jul 29.

Division of Rheumatology, Università Cattolica del Sacro Cuore, Rome, Italy.

COVID-19 pandemia is a major concern for patients and healthcare systems. The fear of infection by patients with concomitant rheumatic diseases (either adult or children) and connective tissue diseases is arising worldwide, because of their immunological background and immunological therapies. Analysing the basic biology of single diseases, the data suggest that there is an "immunological umbrella" that seems to protect against the infection, through IFN type 1 and NK cell function. To date, reports from China, United States and Europe did not reveal an higher risk of infection, either for rheumatoid arthritis, juvenile idiopathic arthritis nor for lupus erythematosus. Antimalarials, anti-IL6-Anti-IL6 receptor, anti-IL1, anti-GM-CSF receptor and JAK1/2/3 inhibitors, are under investigation in COVID-dedicated clinical trials to control the inflammation raised by SARS-CoV-2 infection. Initial reports on the occurrence of autoimmune phenomena in the convalescence phase of SARS-CoV-2 infection suggests that the immunological consequences of the infection need to be strictly understood. Reporting of the study conforms to broad EQUATOR guidelines (Simera et al January 2010 issue of EJCI).
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http://dx.doi.org/10.1111/eci.13342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404583PMC
September 2020

Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis.

Nat Med 2020 08 29;26(8):1295-1306. Epub 2020 Jun 29.

Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), .

Immune-regulatory mechanisms of drug-free remission in rheumatoid arthritis (RA) are unknown. We hypothesized that synovial tissue macrophages (STM), which persist in remission, contribute to joint homeostasis. We used single-cell transcriptomics to profile 32,000 STMs and identified phenotypic changes in patients with early/active RA, treatment-refractory/active RA and RA in sustained remission. Each clinical state was characterized by different frequencies of nine discrete phenotypic clusters within four distinct STM subpopulations with diverse homeostatic, regulatory and inflammatory functions. This cellular atlas, combined with deep-phenotypic, spatial and functional analyses of synovial biopsy fluorescent activated cell sorted STMs, revealed two STM subpopulations (MerTKTREM2 and MerTKLYVE1) with unique remission transcriptomic signatures enriched in negative regulators of inflammation. These STMs were potent producers of inflammation-resolving lipid mediators and induced the repair response of synovial fibroblasts in vitro. A low proportion of MerTK STMs in remission was associated with increased risk of disease flare after treatment cessation. Therapeutic modulation of MerTK STM subpopulations could therefore be a potential treatment strategy for RA.
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http://dx.doi.org/10.1038/s41591-020-0939-8DOI Listing
August 2020

Antimalarial use and arrhythmias in COVID-19 and rheumatic patients: a matter of dose and inflammation?

Ann Rheum Dis 2020 May 18. Epub 2020 May 18.

Division of Rheumatology, IRCCS, Fondazione Policlinico Universitario A Gemelli, Catholic University of the Sacred Heart, Rome, Italy.

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http://dx.doi.org/10.1136/annrheumdis-2020-217828DOI Listing
May 2020

Comprehensive review on intravertebral intraspinal, intrajoint, and intradiscal vacuum phenomenon: From anatomy and physiology to pathology.

Mod Rheumatol 2021 Mar 22;31(2):303-311. Epub 2020 May 22.

Istitute of Rheumatology, Università Cattolica del Sacro Cuore, Roma, Italy.

The term 'vacuum phenomenon' (VP), is characterized by gas-like density areas due to a rapid increase in the joint space volume ('acute VP') or represent a chronic gas collection. It can occur within a collapsed vertebral body, the spinal canal, joints but mainly the intervertebral disc. Studies support that VP is originated by a dynamic process involving the balance between tissues' liquid and gaseous components, influenced by the duration and the depth of mechanical and metabolic alterations, by the nature of neighboring tissues and the variability in both pressure and permeability of disc or vertebral or joint structures. Prevalence of VP in the general population is about 2%, reaching 20% in the elderly with disc degeneration. Although it's often a random finding in asymptomatic patients, VP is an eventually painful expression of disc degeneration, or disc or vertebral fracture, or bone lesions. In sporadic cases, intradiscal gas can be expelled (all-in-one or gradually), resulting in a gaseous cyst, causing pain and neurological symptoms. Considering that spontaneous resolution and recurrence after surgery are both possible, most of the authors recommend conservative treatment in patients with intradiscal and intravertebral VP; occasionally percutaneous CT(computed tomography) -guided aspiration or vertebral stabilization.
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http://dx.doi.org/10.1080/14397595.2020.1764744DOI Listing
March 2021

Checkpoint inhibitors (CPI) and autoimmune chronic inflammatory diseases (ACIDs): tolerance and loss of tolerance in the occurrence of immuno-rheumatologic manifestations.

Clin Immunol 2020 05 30;214:108395. Epub 2020 Mar 30.

Division of Rheumatology, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy. Electronic address:

Immune related adverse events (irAEs) have been observed with all checkpoint inhibitors and are very frequent. The evidences coming from experimental models of congenital or acquired deficiency of CTLA-4 or from PD-1 knock-out mice, provided all the informations to interpret the organ or systemic manifestations (endocrine, or systemic autoimmune chronic inflammatory diseases-ACIDs) observed in trials as well as in registries of cohorts treated with anti-CTLA-4 or anti-PD-1/PD-L1 inhibitors, or combination therapies. Finally the concern raised by cancers occurring in patients with autoimmune diseases (Systemic Lupus Erythematosus, Myositis, Rheumatoid Arthritis, Psoriatic Arthritis, Vasculitis, Scleroderma, Polymyalgia Rheumatica and others) and how to deal with immunotherapy was discussed. The biological knowledges acquired with the immunotherapy trials, have paved to way to better treat autoimmune diseases in patients developing cancer during the autoimmune illness. Immunotherapy without Autoimmunity is the unmet need within our reach in the future.
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http://dx.doi.org/10.1016/j.clim.2020.108395DOI Listing
May 2020

Comment on: Skin improvement is a surrogate for favourable changes in other organ systems in early diffuse cutaneous systemic sclerosis.

Rheumatology (Oxford) 2020 07;59(7):1782-1783

Institute of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy.

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http://dx.doi.org/10.1093/rheumatology/keaa066DOI Listing
July 2020

HBV and targeted synthetic (ts)DMARDs: what have we learned from bDMARDs and tsDMARDs?

RMD Open 2020 02;6(1)

Division of Rheumatology, IRCCS, Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart, Rome, Italy

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http://dx.doi.org/10.1136/rmdopen-2020-001171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046984PMC
February 2020

Is treat-to-target really working in rheumatoid arthritis? a longitudinal analysis of a cohort of patients treated in daily practice (RA BIODAM).

Ann Rheum Dis 2020 04 24;79(4):453-459. Epub 2020 Feb 24.

CaRE Arthritis LTD, University of Alberta, Edmonton, Alberta, Canada.

Objectives: To investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target.

Methods: RA patients from 10 countries starting/changing conventional synthetic or biological disease-modifying anti-rheumatic drugs were assessed for disease activity every 3 months for 2 years (RA BIODAM (BIOmarkers of joint DAMage) cohort). Per visit was decided whether a patient was treated according to a T2T-strategy with 44-joint disease activity score (DAS44) remission (DAS44 <1.6) as the target. Sustained T2T was defined as T2T followed in ≥2 consecutive visits. The main outcome was the achievement of DAS44 remission at the subsequent 3-month visit. Other outcomes were remission according to 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definitions. The association between T2T and remission was tested in generalised estimating equations models.

Results: In total 4356 visits of 571 patients (mean (SD) age: 56 (13) years, 78% female) were included. Appropriate application of T2T was found in 59% of the visits. T2T (vs no T2T) did not yield a higher likelihood of DAS44 remission 3 months later (OR (95% CI): 1.03 (0.92 to 1.16)), but sustained T2T resulted in an increased likelihood of achieving DAS44 remission (OR: 1.19 (1.03 to 1.39)). Similar results were seen with DAS28-ESR remission. For more stringent definitions (CDAI, SDAI and ACR/EULAR Boolean remission), T2T was consistently positively associated with remission (OR range: 1.16 to 1.29), and sustained T2T had a more pronounced effect on remission (OR range: 1.49 to 1.52).

Conclusion: In daily clinical practice, the correct application of a T2T-strategy (especially sustained T2T) in patients with RA leads to higher rates of remission.
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http://dx.doi.org/10.1136/annrheumdis-2019-216819DOI Listing
April 2020

The B side of rheumatoid arthritis pathogenesis.

Pharmacol Res 2019 11 28;149:104465. Epub 2019 Sep 28.

Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy; Institute of Rheumatology, Università Cattolica del Sacro Cuore, Rome, Italy. Electronic address:

In the last years, a dramatic amount of research has been performedincreasing the knowledge about the biological mechanism underpinning Rheumatoid Arthritis (RA) inflammation, putting B lymphocytes in the center of RA pathogenesis. Nowadays, B cell phenotypes and autoantibodies positivity arose as important biomarkers in early and long-standing disease. Moreover, comparative analysis of peripheral blood and synovial tissue compartments enables the identification of novel physiopathological mechanisms promoting inflammation. In this narrative review we will discuss the biological relevance of B cell derived autoimmunity and in RA course, from disease onset to remission achievement.
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http://dx.doi.org/10.1016/j.phrs.2019.104465DOI Listing
November 2019

Adherence to Treat-to-target Management in Rheumatoid Arthritis and Associated Factors: Data from the International RA BIODAM Cohort.

J Rheumatol 2020 06 15;47(6):809-819. Epub 2019 Sep 15.

From the Department of Rheumatology, Leiden University Medical Center, Leiden; Zuyderland Medical Center, Heerlen; Academic Medical Center/University of Amsterdam, Amsterdam University Medical Center, Amsterdam; Amsterdam Rheumatology and Immunology Center, locations Reade and Amsterdam, University Medical Center, Amsterdam, the Netherlands; Newman Clinical Research, Department of Rheumatology, St. Vincent's University Hospital, Dublin, Ireland; Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet - Glostrup, University of Copenhagen, Copenhagen, Denmark; University of Alberta, Edmonton, Alberta; The Arthritis Program Research Group, Newmarket, Ontario; Divisions of Rheumatology and Clinical Immunology and Allergy, McMaster University, Hamilton, Ontario; Rheumatology Department, Centre Intégré Universitaire en Santé et Services Sociaux (CIUSSS) de l'Estrie-Centre Hospitalier Universitaire de Sherbrooke (CHUS), Université de Sherbrooke, Sherbrooke, Quebec; Departments of Medicine and Community Health Services, Cumming School of Medicine, University of Calgary, Calgary, Alberta; CaRE Arthritis Ltd., Edmonton, Alberta, Canada; Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Divisions of Rheumatology and Internal Medicine, Catholic University of the Sacred Heart, Rome; Department of Rheumatology, Università di Verona, Verona; St. Anna Hospital, Ferrara (loc. Cona); Department of Rheumatology, Istituto Ortopedico Gaetano Pini, Milan, Italy; Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany; Departement de rhumatologie, Université de Montpellier, Centre Hospitalier Universitaire (CHU) Montpellier, Montpellier; Service de rhumatologie, Centre National de Référence des Maladies Autoimmunes Rares de l'Adulte CERAINO, and UMR1227, Lymphocytes B et Autoimmunité (LBAI), Université de Brest, INSERM, LabEx Immunothérapies Grand Ouest (IGO), Brest; Paris Descartes University, Rheumatology Department, Cochin Hospital, AP-HP, INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris; Centre de Rhumatologie, Hôpital Pierre Paul Riquet - Purpan, CHU de Toulouse, Toulouse; Service de Rhumatologie, CHU Bordeaux Pellegrin, Bordeaux, France; Divisions of Rheumatology and Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, Maryland, USA; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.

Objective: Compelling evidence supports a treat-to-target (T2T) strategy for optimal outcomes in rheumatoid arthritis (RA). There is limited knowledge regarding the factors that impede implementation of T2T, particularly in a setting where adherence to T2T is protocol-specified. We aimed to assess clinical factors that associate with failure to adhere to T2T.

Methods: Patients with RA from 10 countries who were starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required per protocol to adhere to the T2T strategy. Factors influencing adherence to T2T low disease activity (T2T-LDA; 44-joint count Disease Activity Score ≤ 2.4) were analyzed in 2 types of binomial generalized estimating equations models: (1) including only baseline features (baseline model); and (2) modeling variables that inherently vary over time as such (longitudinal model).

Results: A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. Failure of adherence to T2T-LDA was noted in 1765 visits (40.5%). In the baseline multivariable model, a high number of comorbidities (OR 1.10, 95% CI 1.02-1.19), smoking (OR 1.32, 95% CI 1.08-1.63) and high number of tender joints (OR 1.03, 95% CI 1.02-1.04) were independently associated with failure to implement T2T, while anticitrullinated protein antibody/rheumatoid factor positivity (OR 0.63, 95% CI 0.50-0.80) was a significant facilitator of T2T. Results were similar in the longitudinal model.

Conclusion: Lack of adherence to T2T in the RA BIODAM cohort was evident in a substantial proportion despite being a protocol requirement, and this could be predicted by clinical features. [Rheumatoid Arthritis (RA) BIODAM cohort; ClinicalTrials.gov: NCT01476956].
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http://dx.doi.org/10.3899/jrheum.190303DOI Listing
June 2020

QT and QT dispersion intervals in long-standing and moderately active rheumatoid arthritis: results from a multicentre cross-sectional study.

Clin Exp Rheumatol 2020 May-Jun;38(3):516-522. Epub 2019 Aug 27.

UOC di Cardiologia Clinica e Interventistica, Azienda Ospedaliero-Universitaria di Sassari, Italy.

Objectives: To define the prevalence of prolonged QT interval and QT dispersion (QTd) in rheumatoid arthritis (RA) patients and in a control population.

Methods: QT interval corrected by Bazett's formula (QTc) was calculated from standard 12-lead ECGs in 963 subjects free of previous cardiovascular events (646 RA patients and 317 controls strictly matched for age, sex and cardiovascular risk factors).

Results: RA patients (59.6±9.6 years, 68.1% females) had a long mean disease duration (10.6 years) and moderate disease activity (DAS28=3.68±1.23). QTc was 5 msec longer in RA patients than in controls (412±9 vs. 407±28 msec, p=0.013). However, the prevalence of QTc prolongation in RA patients and controls was not significantly different (5.3% vs. 6.3%, p=0.50). On the contrary, RA patients had a significantly greater QTd (42±26 vs. 35±18 msec, p<0.001) and a higher prevalence of increased QTd (33.3% vs. 18.3%, p<0.001) than controls. Furthermore, RA was independently associated to increased QTd [OR(95%CI)= 2.21(1.58-3.08), p=0.0001]. In the RA population, male gender and older age were independently associated with a higher prevalence of prolonged QTd.

Conclusions: In this cohort of long-standing and moderately active RA patients, RA showed longer QTc but similar prevalence of prolonged QTc and an increased QTd with a 1.8-fold higher prevalence of increased QTd than the control population. Further studies in larger prospective cohorts are warranted to investigate whether QTd prolongation predicts sudden cardiac death and other adverse cardiovascular outcomes in RA.
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September 2020

Outcomes and Findings of the International Rheumatoid Arthritis (RA) BIODAM Cohort for Validation of Soluble Biomarkers in RA.

J Rheumatol 2020 06 1;47(6):796-808. Epub 2019 Sep 1.

From the Departments of Medicine and Radiology, University of Alberta; CaRE Arthritis Ltd., Edmonton, Alberta; The Arthritis Program Research Group, Newmarket, Ontario; Divisions of Rheumatology and Clinical Immunology and Allergy, McMaster University, Hamilton, Ontario; Departments of Medicine and Community Health Services, Cumming School of Medicine, University of Calgary, Calgary, Alberta; Rheumatology Department, CIUSSS de l'Estrie-CHUS, Université de Sherbrooke, Sherbrooke, Quebec, Canada; Department of Rheumatology, St. Vincent's University Hospital, Dublin, Ireland; Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet - Glostrup, University of Copenhagen, Copenhagen, Denmark; Department of Rheumatology, Leiden University Medical Center, Leiden; Zuyderland Medical Center, Heerlen; Academic Medical Center/University of Amsterdam, Amsterdam University Medical Center, Amsterdam, the Netherlands; Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Divisions of Rheumatology and Internal Medicine, Catholic University of the Sacred Heart, Rome; Department of Rheumatology, Università di Verona, Verona; St. Anna Hospital, Ferrara (loc. Cona); Department of Rheumatology, Istituto Ortopedico Gaetano Pini, Milan, Italy; Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany; Departement de rhumatologie, Université de Montpellier, CHU Montpellier, Montpellier; Service de rhumatologie, CHU Brest, and Lymphocyte B et Autoimmunité (LBAI), U1227, Université de Brest, INSERM, F-29200 Brest; Paris Descartes University, Rheumatology Department, Cochin Hospital, AP-HP, INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris; Centre de Rhumatologie, Hôpital Pierre Paul Riquet - Purpan, CHU de Toulouse, Toulouse; Service de Rhumatologie, CHU Bordeaux Pellegrin, Bordeaux, France; Divisions of Rheumatology and Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, Maryland, USA; Amsterdam Rheumatology and Immunology Center, locations Reade and Amsterdam, University Medical Center, Amsterdam, the Netherlands; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.

Objective: The Outcome Measures in Rheumatology Soluble Biomarker Working Group initiated an international, multicenter, prospective study, the Rheumatoid Arthritis (RA) BIODAM cohort, to generate resources for the clinical validation of candidate biomarkers predictive of radiographic progression. This first report describes the cohort, clinical outcomes, and radiographic findings.

Methods: Patients with RA from 38 sites in 10 countries starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required to adhere to a treat-to-target strategy. Biosamples (serum, urine) were acquired every 3 months, radiography of hands and feet every 6 months, and ultrasound of hands and feet every 3 months in a subset. Primary endpoint was radiographic progression by the Sharp/van der Heijde score.

Results: A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. At baseline, the majority was female (76%), mean age 55.7 years, and mean disease duration 6.5 years. Patients had a mean of 8.4 swollen and 13.6 tender joints, 44-joint count Disease Activity Score (DAS44) 3.8, 77.7% rheumatoid factor-positive or anticitrullinated protein antibody-positive. Percentage of patients in DAS and American College of Rheumatology remission at 2 years was 52.2% and 27.1%, respectively. Percentage of patients with radiographic progression (> 0.5) at 1 and 2 years was 38.2% and 59.9%, respectively.

Conclusion: The RA BIODAM prospective study succeeded in generating an extensive list of clinical, imaging (2343 radiographs), and biosample (4638 sera) resources that will be made available to expedite the identification and validation of biomarkers for radiographic damage endpoints. (Clinicaltrials.gov: NCT01476956, clinicaltrials.gov/ct2/show/NCT01476956).
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http://dx.doi.org/10.3899/jrheum.190302DOI Listing
June 2020

Measuring the T-cell down-regulation of TCR-zeta, ZAP-70 and CD28 in arthritis patients: An old tool for new biomarkers.

Eur J Immunol 2019 12 22;49(12):2195-2203. Epub 2019 Aug 22.

Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli - Catholic University of the Sacred Heart, Rome, Italy.

Low T-cell receptor (TCR)/CD28 signaling lymphocytes are expanded in arthritis. We asked whether the down-expression of TCR-related molecules correlates with specific arthritis characteristics and if it has clinical implications. TCR-ZETA, ZAP-70 and CD28 expression was measured by flow cytometry in synovial fluid (SF) and peripheral blood (PB)-derived T cells. In PB, ZETA-downregulation in CD4 CD28 and consequent CD4 CD28lowZETAlow cell expansion correlate with CRP elevation, leukocyte recruitment into SF and, primarily, disease activity (DAS). In some patients, ZETA-downregulation extends to CD8 CD28null and/or CD8 CD28 cells, and this correlates with enhanced leukocyte recruitment, multiple joint involvement, and disability index (HAQ). ZETA-downregulation in CD4 CD28 may also lead to CD4 CD28 ZETAnull cell expansion, which strongly correlates with HAQ. In SF, ZETA-downregulation in CD8 CD28null and consequent CD8 CD28nullZETAlow/null cell expansion correlate with CRP elevation and neutrophilic influx into SF, whereas ZAP-downregulation in CD8 CD28 and consequent CD8 CD28lowZAPlow cell expansion strongly correlate with HAQ and DAS. ZETA-downregulation is preponderant in SF of seronegative arthritides, with seronegative rheumatoid arthritis showing significant down-regulation in CD8 CD28null, and non-rheumatoid arthritides showing significant down-regulation in CD4 CD28 . Altogether, we identified new molecular and cellular biomarkers of arthritis-related T-cell inflammation, useful for assessing arthritis activity, predicting polyarticular progression and functional impairment, characterizing seronegative arthritides, and possibly tailoring immunotherapies.
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http://dx.doi.org/10.1002/eji.201847849DOI Listing
December 2019

Overweight/obesity affects histological features and inflammatory gene signature of synovial membrane of Rheumatoid Arthritis.

Sci Rep 2019 07 18;9(1):10420. Epub 2019 Jul 18.

Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Overweight/obesity influence disease burden and clinical outcome of Rheumatoid Arthritis (RA). The impact of overweight/obesity on synovial tissue (ST) inflammation is largely unknown. Here, we investigated the histological and transcriptional signature of ST obtained from RA in different disease phases (disease onset, failure to first-line conventional DMARDs and in sustained clinical and ultrasound remission) finding that overweight/obese DMARDs naive RA showed higher likelihood of follicular synovitis, higher IHC scores for sublining inflammatory cells (CD68, CD21 and CD20) and higher IL-1RA plasma levels than normal weight RA. Regardless to the synovitis pattern, overweight/obese DMARDs naive RA showed a worse clinical response to "Treat-to-target" (T2T) than normal weight RA at 6 and 12 months follow-up. Conversely, MTX-IR RA did not show significant differences in synovial inflammation based on BMI category. Overweight/obese RA in stable clinical and US remission showed higher degree of residual synovitis in terms of sublining CD68, CD20 cells and lining and sublining CD3 compared to normal weight RA. Finally, gene expression profile analysis revealed that ST of overweight/obese DMARDs naive RA is enriched by CCL3 and MyD88 compared to normal weight RA in sustained disease remission, the latter correlating with BMI and IHC scores for synovial CD68 cells. These findings suggest that indeed overweight/obese RA show higher degree of synovitis at disease onset and after remission achievement that influences the response rate to T2T and should be considered within the management of patients with RA.
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http://dx.doi.org/10.1038/s41598-019-46927-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639364PMC
July 2019

JAK inhibition by methotrexate (and csDMARDs) may explain clinical efficacy as monotherapy and combination therapy.

J Leukoc Biol 2019 11 16;106(5):1063-1068. Epub 2019 Jul 16.

Institute of Rheumatology, Università Cattolica del Sacro Cuore, Rome, Italy.

Methotrexate (MTX) is recognized as the anchor drug in the algorithm treating chronic arthritis (RA, psoriatic arthritis), as well as a steroid sparing agent in other inflammatory conditions (polymyalgia rheumatica, vasculitis, scleroderma). Its main mechanism of action has been related to the increase in extracellular adenosine, which leads to the effects of A2 receptor in M1 macrophages that dampens TNFα and IL12 production and increases IL1Ra and TNFRp75. By acting on A2 receptor on M2 macrophages it enhances IL10 synthesis and inhibits NF-kB signaling. MTX has also been shown to exert JAK inhibition of JAK2 and JAK1 when tested in Drosophila melanogaster as a model of kinase activity and in human cell lines (nodular sclerosis Hodgkin's lymphoma and acute myeloid leukemia cell lines). These effects may explain why MTX leads to clinical effects similar to anti-TNFα biologics in monotherapy, but is less effective when compared to anti-IL6R in monotherapy, which acting upstream exerts major effects downstream on the JAK1-STAT3 pathway. The MTX effects on JAK1/JAK2 inhibition also allows to understand why the combination of MTX with Leflunomide, or JAK1/JAK3 inhibitor leads to better clinical outcomes than monotherapy, while the combination with JAK1/JAK2 or JAK1 specific inhibitors does not seem to exert additive clinical benefit.
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http://dx.doi.org/10.1002/JLB.5RU0519-145RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852123PMC
November 2019

Body mass index and treatment response to subcutaneous abatacept in patients with psoriatic arthritis: a analysis of a phase III trial.

RMD Open 2019 30;5(1):e000934. Epub 2019 May 30.

Swedish Medical Center and University of Washington, Seattle, Washington, USA.

Objective: This analysis of the phase III Active PSoriaTic Arthritis RAndomizEd TriAl (ASTRAEA) evaluated the effect of baseline body mass index (BMI) on subsequent response to subcutaneous (SC) abatacept in patients with psoriatic arthritis (PsA).

Methods: In ASTRAEA, patients with active PsA were randomised (1:1) to receive blinded weekly SC abatacept 125 mg or placebo for 24 weeks. Treatment response at week 24 was assessed by the proportions of patients achieving American College of Rheumatology 20% improvement response, Disease Activity Score in 28 joints (DAS28 (C reactive protein (CRP))) ≤3.6 and <2.6, Health Assessment Questionnaire-Disability Index reduction from baseline ≥0.35 and radiographic non-progression (defined as change from baseline ≤0 in PsA-modified total Sharp/van der Heijde score). Responses were stratified by baseline BMI (underweight/normal, <25 kg/m; overweight, 25-30 kg/m; obese, >30 kg/m) and compared in univariate and multivariate models.

Results: Of 212/213 and 210/211 patients with baseline BMI data in the abatacept and placebo groups, respectively, 15% and 19% were underweight/normal, 36% and 27% were overweight, and 49% and 54% were obese. After adjusting for baseline characteristics, there were no significant differences for any outcome measure at week 24 with abatacept in the overweight or obese versus underweight/normal subgroup. In the placebo group, patients in the obese versus underweight/normal subgroup were significantly less likely to achieve DAS28 (CRP) <2.6 at week 24 (OR 0.26; 95% CI 0.08 to 0.87; p=0.03).

Conclusion: BMI does not impact clinical or radiographic response to SC abatacept in patients with PsA.

Trial Registration Number: NCT01860976.
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http://dx.doi.org/10.1136/rmdopen-2019-000934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560664PMC
April 2020

Body mass index as a driver of selection of biologic therapy in rheumatoid arthritis. Results from the US-CLARA study.

Eur J Intern Med 2019 Aug 18;66:57-61. Epub 2019 May 18.

Rheumatology Unit, Catholic University of the Sacred Heart, Rome, Italy. Electronic address:

Purpose: Body mass index (BMI) demonstrated to influence the clinical response to different drugs in rheumatoid arthritis (RA). The aim of this study was to investigate the role of BMI in the achievement of remission in active RA patients starting the treatment with abatacept.

Methods: Data regarding 130 RA patients enrolled in the UltraSound-CLinical ARthritis Activity (US-CLARA) study were retrospectively analyzed. Patients were assessed at baseline (when starting abatacept treatment) and at 3- and 6-months. An extensive clinimetric evaluation, including a new ultrasound (US)/clinical composite disease activity index, termed US-CLARA, was performed at every timepoints. Outcome of interest of the study was the impact of BMI on the achievement of the Disease Activity Score 28-joints erythrocyte sedimentation rate (DAS28-ESR) or the ACR/EULAR Boolean remission criteria at 6 month.

Results: At 6-month 26 out of 130 patients were defined as responders to abatacept. Comparing the baseline characteristics of responders to non-responders, US-CLARA showed a statistically significant difference between the two groups. The logistic regression analysis showed that the two indipendent variables, predictive of treatment response (keeping the DAS28-ESR and/or Boolean remission criteria as dependent variable), were the self-tender joint count assessment (p = 0.0412) and the ultrasound score (p = 0.0211). No other baseline variable, notably BMI, was associated to 6-month abatacept response.

Conclusions: BMI does not influence the abatacept response in RA patients with active disease. During abatacept treatment, the clinical response can be achieved despite a condition of overweight or obesity.
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http://dx.doi.org/10.1016/j.ejim.2019.05.017DOI Listing
August 2019

Differential synovial tissue biomarkers among psoriatic arthritis and rheumatoid factor/anti-citrulline antibody-negative rheumatoid arthritis.

Arthritis Res Ther 2019 05 9;21(1):116. Epub 2019 May 9.

Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Background: Differential diagnosis among psoriatic arthritis (PsA) and seronegative rheumatoid arthritis (Ab RA) can be challenging particularly in the clinical setting of peripheral phenotype and autoantibodies seronegativity. The aim of the study was to identify synovial tissue (ST) biomarkers differentially expressed in PsA and Ab RA and test their predictive value of therapeutic response.

Methods: Thirty-four PsA patients [12 DMARD naive and 22 non-responder to methotrexate (MTX-IR)] with peripheral joint involvement and 55 Ab RA (27 DMARD naive and 28 MTX-IR) underwent US-guided ST biopsy and immunohistochemistry (IHC) for CD68, CD3, CD20, CD21, CD117, and CD138 cells. After study entry, each DMARD-naive patient started MTX therapy and was followed in an outpatient setting for at least 6 months to define the achievement of Minimal Disease Activity (PsA) and DAS remission (Ab RA) status respectively. Each IR-MTX patient was treated according to EULAR recommendations.

Results: At study entry, IHC analysis revealed that PsA patients had comparable levels of lining and sublining CD68 and sublining CD21, CD20, and CD3 cells than Ab RA, despite the therapeutic regimen. Moreover, regardless of the therapeutic scheme, PsA patients showed higher IHC score of CD117 cells (p = 0.0004 and p = 0.0005 for naive and MTX-IR patients respectively) compared to Ab RA patients. Conversely, Ab RA patients showed higher IHC score of CD138 cells, irrespective to the therapeutic scheme (p = 0.04 and p = 0.002 for naive and MTX-IR patients respectively). Analyzing the response rate to the therapeutic scheme, naive PsA patients reaching MDA status at 6 months follow-up, showed, at the study entry, lower IHC score of CD3 cells compared to PsA patients not reaching this outcome (p = 0.02); conversely, naive Ab RA patients reaching DAS remission status at 6 months follow-up, showed, at the study entry, lower IHC score of sublining CD68 cells compared to Ab RA patients not reaching this outcome (p < 0.001).

Conclusions: CD117 and CD138 cells are differentially distributed among PsA and Ab RA. Histological analysis of ST may help to solve the clinical overlap between the two diseases and provides prognostic data about the therapy success.
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http://dx.doi.org/10.1186/s13075-019-1898-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509792PMC
May 2019